1. Field of the Invention
The present invention relates generally to time-resolved spectroscopy and, more specifically, to time-resolved spectroscopy using pseudo-random modulated diode lasers. More particularly, the invention relates to a high time and space resolution system and method in relation with the imaging and characterization of fluoresces sources or optically diffused media.
2. Description of the Related Art
Time-resolved optical sensing, such as, fluorescence spectroscopy and near infra-red spectroscopy (NIRS), are well known in the art. Conventional time resolved spectroscopy relies on a high-power, short pulse laser system, which excites the molecular states instantaneously in comparison to slow fluorescent decay or provides an impulse for photon migration within a scattering medium. The short pulse durations in the laser systems are in the picosecond range and a fast data acquisition system is used in measuring the fluorescence of the object scanned with the laser system. Current data acquisition systems have a sufficient resolution and signal to noise ratio; unfortunately, these pulsed systems are in limited use due to their complexity, size, and cost. Generally, the system consists of a high power picosecond laser(s), sophisticated optics, complex electronics and elaborate high speed data systems. The systems are large in size and weight, expensive, and prone to frequent breakdowns in operation, thus requiring the attendance of highly trained personnel. Consequently, there is serious difficult in using the system for autonomous operation in clinical medicine and biochemical applications.
Phase Modulated Spectroscopy (PMS) is another method used in indirect pathlength resolved NIRS measurement. This method uses modulation-phase-delay measurement, which uses an image intensifier and a mode locked picosecond laser system, over a wide range of frequency variations. This method, however, has several drawbacks. First, the measurement does not provide information on the fluorescent efficiency, which is as important as the fluorescence decay time. Second, the sensitivity of the technique has only one optimum point for a given decay constant, due to the opposite trends between the changes of the modulation depth and the phase angle value as a function of the modulation frequency. Importantly, this method assumes a simple exponential decay of the signal in the interpretation of the data, which is not a trivial assumption for the in-vivo sense applications. When the decay profile deviates from the exponential function, the data cannot be readily resolved to retrieve the true decay profile.
Time-resolved spectroscopy is used to replace more traditional methods of noninvasive medical detection techniques, such as x-rays. Currently, x-ray examinations provide excellent detection techniques in many situations. One such situation is in mammography. X-ray mammography is used for identifying micro calcifications-calcium pockets at the center of tumors, which pockets may be early indicators of breast cancers. Despite its success, however, x-ray mammography has certain disadvantages such as the potential danger from ionizing radiation, the possibility of triggering cancer in tissue cells, and the difficulty of detecting ultra small growths in the early stages. As an alternative to x-ray techniques, non-ionizing approaches, such as near-ir photonics are being used for imaging ultra small tumors of one millimeter or less in size.
Tissue absorption is comparatively low in the red and near-ir spectral region between, about 600 nanometers (nm), where blood absorption falls off strongly, and 1.3 .mu.meters, where water absorption increases rapidly. Transillumination technique for breast diagnostics has been demonstrated for sometime, but its value has been limited because of strong image blurring due to heavy multiple scattering by the tissue. To make this technique more useful, a number of methods for compressing the scattered light are considered. One such technique is time-gated spectroscopy. In this technique, picosecond laser pulses are transmitted through the tissue and the time gated-photons are detected using a fast optical gate such as a Kerr-cell. This method allows differentiation of three different components of the migrated photons through the tissue: ballistic component, snake-like component, and diffuse component. The ballistic component results from the coherent interference of the light scattered in the forward direction and the photons propagated nearly straight through, thus resulting in the least time delay. The ballistic component always exists, but its intensity is very low. In an inhomogeneous medium, some photons are scattered slightly off the straight line path and zig zag through the medium. This is the snake-like component (quasi-coherent). The diffuse component is the most dominant part of the transmitting photons and the delay is the greatest. Time-gating provides a means of differentiating these components in terms of delay time associated with each component. Currently, this technique has shown to be able to resolve an image imbedded in a highly scattered medium with a resolution up to one millimeter.
Another approach to time-gating the transilluminated photons is the use of frequency-domain measurements, which are well known in the art. In this method, the time delay of the migrating photons are measured indirectly in terms of the mode-locked picoseconds pulse trains in the tissue. This technique has been extensively developed for time resolved fluorescent measurements. However, the measurement results are uncertain in terms of an unusual frequency response curve of the phase angle plot, as well as difficulty in curve fitting the results to a theoretical prediction. This is based on the assumption of exponential decay of the impulse response function, as well as difficulty of unfolding the signature of the nonexponential components of the impulse response function, which is more likely in most of the in-vivo samples of small size.
Accordingly, what is needed as an improved apparatus for time-resolved spectroscopy that does not require the sophisticated optics, complex electronics, or elaborate high-speed data systems of prior time-resolved spectroscopy apparatus. Further, the improved apparatus should be able to overcome the problems associated with the assumption of a simple exponential decay of the signal for any problems associated with back ground lighting existing in pulse systems. Additionally, adverse health concerns to the patient should be reduced while approaching the diagnostic accuracy of the x-ray measurement techniques without resorting to ionization.